期刊
HUMAN MOLECULAR GENETICS
卷 20, 期 19, 页码 3738-3745出版社
OXFORD UNIV PRESS
DOI: 10.1093/hmg/ddr290
关键词
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资金
- France Alzheimer
- CNRS
- INSERM
- French Ministry of Research and Technology
- FUI grant
- Region Haute-Normandie
The microtubule-associated protein Tau is found in large amount in axons of neurons and is involved in human neurodegenerative diseases called tauopathies, which include Alzheimer's disease. In these diseases, the Tau protein is abnormally hyperphosphorylated and one therapeutic strategy currently under consideration consists in inhibiting Tau phosphorylation. However, the consequences of an excess of hypophosphorylated Tau onto neuronal physiology have not been investigated in vivo. Here we studied how important is Tau phosphorylation for axonal transport and neurohormone release in vivo, using the Drosophila model. Surprisingly, our results demonstrate a stronger toxicity of hypophosphorylated Tau for neuronal function, when compared with normal or pseudophosphorylated Tau. This reveals a potential limit of the current therapeutic strategy aimed at inhibiting Tau phosphorylation.
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